Bradykinin receptors (B1, B2) are GPCRs that have been implicated in the proliferative and fibrotic response that characterizes diabetic nephropathy. Bradykinin receptor expression is increased in the diabetic glomerulus, and their activation initiates transcription of the pro-fibrotic genes: CTGF and TGF2R1. Co-immunoprecipitation and fluorescent colocalization studies have shown that the B2 receptor forms heterodimers with the angiotensin 2 type 1 (AT1R) receptor on the plasma membrane. AT1-B2 heterodimer formation potentiates calcium signaling which may aggravate the fibrotic response. We hypothesize that elevated expression of the AT1R increases the population of AT1-B2 heterodimers, and promotes bradykinin- independent internalization of B2 receptors by SII[Sar1, Ile4, Ile8]-angiotensin (a peptide antagonist of the AT1R that causes 2-arrestin dependent internalization without coupling to G proteins) but not by losartan (a non-peptide neutral antagonist). In an AT1R tetracycline-inducible HEK cell model, SII pretreatment was a non- competitive antagonist of bradykinin-induced calcium signaling whereas losartan had no effect. Similar results were obtained in primary rat VSMCs. We hypothesize that AT1R antagonists that induce receptor internalization can function as allosteric antagonists of bradykinin signaling in conditions that favor the formation of heterodimers, suggesting their utility in the prevention of diabetic nephropathy progression.